The advent of soluble common gamma chain rocks the T cell world: A novel therapeutic target for autoimmune diseases

The common gamma chain (γc) is the central signaling unit for the γc cytokine receptor family. γc cytokine signaling is mainly regulated by cytokine-specific receptor alpha chain expression levels but not γc expression levels. Here we will highlight that a soluble form of γc (sγc) expression, which is generated by alternative splicing, impairs naive T cell survival and promotes inflammation in a manner of inhibiting IL-7 and IL-2 signaling, representatively. Furthermore, sγc expression is significantly enhanced upon T cell activation. sγc enhances in vitro and in vivo Th17 differentiation through dampening of IL-2 signal, and sγc-overexpressing mice are consequently more susceptible to EAE. Therefore, sγc is a novel immunoregulator that control T cell biology by regulation of γc cytokine signaling.